Hard conditions of long-term manned spaceflight can affect functions of many biological systems including a system of drug metabolism. The cytochrome P450 (CYP) superfamily plays a key role in the drug metabolism. In this study we examined the hepatic content of some P450 isoforms in mice exposed to 30 days of space flight and microgravity. The CYP content was established by the mass-spectrometric method of selected reaction monitoring (SRM). Significant changes in the CYP2C29, CYP2E1 and CYP1A2 contents were detected in mice of the flight group compared to the ground control group. Within seven days after landing and corresponding recovery period changes in the content of CYP2C29 and CYP1A2 returned to the control level, while the CYP2E1 level remained elevated. The induction of enzyme observed in the mice in the conditions of the spaceflight could lead to an accelerated biotransformation and change in efficiency of pharmacological agents, metabolizing by corresponding CYP isoforms. Such possibility of an individual pharmacological response to medication during long-term spaceflights and early period of postflight adaptation should be taken into account in space medicine.
Objective
Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA).
Methods
Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis.
Results
Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3–3.3 µM], P <.01) and the PIN (1.9 µM [1.2–6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6–1.4 µM]) group. Plasma sarcosine had “good” and “very good” discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH.
Conclusion
Plasma sarcosine measured by GC-MS had “good” and “very good” classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.
Metabolomics is a promising technology for the application of translational medicine to cardiovascular risk. Here, we applied a liquid chromatography/tandem mass spectrometry approach to explore the associations between plasma concentrations of amino acids, methylarginines, acylcarnitines, and tryptophan catabolism metabolites and cardiometabolic risk factors in patients diagnosed with arterial hypertension (HTA) (n = 61), coronary artery disease (CAD) (n = 48), and non-cardiovascular disease (CVD) individuals (n = 27). In total, almost all significantly different acylcarnitines, amino acids, methylarginines, and intermediates of the kynurenic and indolic tryptophan conversion pathways presented increased (p < 0.05) in concentration levels during the progression of CVD, indicating an association of inflammation, mitochondrial imbalance, and oxidative stress with early stages of CVD. Additionally, the random forest algorithm was found to have the highest prediction power in multiclass and binary classification patients with CAD, HTA, and non-CVD individuals and globally between CVD and non-CVD individuals (accuracy equal to 0.80 and 0.91, respectively). Thus, the present study provided a complex approach for the risk stratification of patients with CAD, patients with HTA, and non-CVD individuals using targeted metabolomics profiling.
Background
Although the post-mortem increase of ammonium in biological fluids is well known, ammonium analysis in vitreous humour has never been used in recent times for the determination of the post-mortem interval. The present work represents a new application of capillary electrophoresis with indirect UV detection in the field of forensic analysis.
Methods
The electrophoretic separation was carried out in a running buffer made of 5 mM imidazole, 5 mM 18-crown-6 ether and 6 mM d,l-α-hydroxybutyric acid (HIBA). To overcome the lack of optical absorption of ammonium, indirect UV detection was applied. The used wavelength was 214 nm.
Results
The method showed good linearity in the concentration range from 0.16 to 5.0 mM. The limit of detection, 0.039 mmol/L, was established on the basis of the linearity curve. Precision and bias studies carried out on the pure ammonium solutions and in real biological samples, revealed %RSDs well below 20%. A preliminary application to real cases where the death time was precisely known (14 bodies) was carried out plotting vitreous humour ammonium vs. post-mortem interval with a resulting good linear correlation until 100 h post-mortem.
Conclusions
After validation in real cases, the present method can become a powerful tool to unravel one of the most challenging issues of forensic investigation: determination of the time of death.
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